kevin letz dnp, mba, msn, rn, cen, fnp-c, pnp-bc, anp -bc
TRANSCRIPT
Kevin Letz DNP, MBA, MSN, RN, CEN, FNP-C, PNP-BC, ANP-BC
Course Objectives: Upon completion of this presentation, the attendee will be able to: 1. Identify the newest diagnostic criteria for anaphylaxis 2. Identify the various signs and symptoms of anaphylaxis 3. Identify the most common triggers and mechanism of anaphylaxis 4. Be familiar with the treatment strategies for anaphylaxis
Multi-system syndrome involving cutaneous, gastrointestinal, respiratory, cardiovascular systems
Resulting from mast cell mediator release Acute onset Severity varies from mild to fatal attacks
Epinephrine Tourniquet O2 , airway maintenance IV fluids Diphenhydramine + cimetidine Vasopressors: dopamine Glucagon
< 10 kg consult resource 10-25 kg = 0.15 mg >25 kg = 0.30 mg Can dose up to 0.5 mg 1:1000 Solution IM
Anyone with Anaphylaxis Hx Persons who have not
experienced but are at increased risk
Always Rx in conjunction with an emergency plan
Sicherer SH, et al. J Allergy Clin Immunol. 2001;108:128-132.
* *
*
* *
1st reaction 2nd reaction 3rd reaction
Severe Epinephrine Severe Epinephrine
Peanuts Tree Nuts
60
50
40
30
20
10
0
Perc
ent
*Indicates a reaction more severe than the previous reaction. 8
There is no absolute contraindication to the administration of epinephrine for anaphylaxis
It is unclear whether patients taking β-blockers are at increased risk of having an anaphylactic event, but they may worsen the event and complicate treatment
Anaphylaxis in patients taking β-blockers may be more severe and difficult to treat because of a reduced β-adrenergic response and an increased alpha-adrenergic response
Achieving high plasma and tissue concentration is critical for reversal of hypotension IM in Vastus Lateralis leads to peak plasma concentration
Simons Fe, Gu X, and Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection.
J Allergy Clin Immunol. 2001 Nov;108(5):871-3.
0 5
10 15 20 25 30 35 40 45 50
SC Epinephrine IM Epinephrine
Adapted from Simons FER, et al. J Allergy Clin Immunol. 1998;101:33-37.
Time to Cmax After Injection (minutes)
P<.05
Min
utes
SC=subcutaneous. 12
Median time to respiratory or cardiac arrest: 30 minutes for food 15 minutes for venom 5 minutes for iatrogenic reactions
260 240 220 200 180 160 140 120 100
80 60 40 20
0
Simons FER, et al. J Allergy Clin Immunol. 2001;108:1040-1044.
Tim
e (s
econ
ds)
Parents Physicians General Duty Nurses
Emergency Dept Nurses
Controls
P<.05 vs all control groups
14
15 Available at: http://www.epipen.com/professionals/about-epipen/auto-injector 15
16 16
http://www.auvi-q.com/demo-video
Common Side Effects: Rapid HR Sweating Shakiness Headache Paleness Nervousness, anxiety, over excitement Weakness Dizziness N/V Breathing Problems
Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol. 2010;10:354-361.
↑ Vasoconstriction ↑ Peripheral vascular
resistance ↓ Mucosal edema
↓ Insulin release ↓ Norepinephrine release
↑ Inotropy ↑ Chronotropy
↑ Bronchodilation ↑ Vasodilation ↑ Glycogenolysis ↓ Mediator release
α1-adrenergic receptor
α2-adrenergic receptor
β1-adrenergic receptor
β2-adrenergic receptor
Epinephrine
18
19
Biphasic reactions Occur in 1% to 23% of patients Can be less severe, equally severe, or more
severe than the initial reaction, ranging in degree from mild symptoms to fatal reactions
The second response usually occurs within 10 hours after resolution of the initial response
Mehr S, et al. Clin Exp Allergy. 2009;39(9):1390-1396. Scranton SE, et al. J Allergy Clin Immunol. 2009;123(2):493-498. Tole JW, Lieberman P. Immunol Allergy Clin North Am. 2007;27(2):309-326. 19
Patie
nts (
%)
Korenblat P, et al. Allergy Asthma Proc. 1999;20:383-386. Varghese M, Lieberman P. J Allergy Clin Immunol. 2006;117(2, suppl): Abstract 1178. S305. Haymore BR, et al. Allergy Asthma Proc. 2005;26(5):361-365. Uguz A, et al. Clin Exp Allergy. 2005;35:746-750. Kelso JM. J Allergy Clin Immunol. 2006;117(2):464-465.
Patients Requiring >1 Dose of Epinephrine
36 33
25
18 16
0 5
10
15 20 25 30
35 40
Korenblat (1999)
Varghese (2006)
Haymore (2006)
Uguz (2005)
Kelso (2006)
20
100 families of food-allergic children evaluated Only 55% of the families had unexpired epinephrine on hand at the time
of the survey Only 32% of children and 18% of pediatricians able to use device
correctly
100 physicians assessed for knowledge of an auto-injector The majority of doctors did not know how to use an auto-injector In 30% of cases, the demonstration would not have delivered
epinephrine to a patient
Sicherer SH, et al. Pediatrics. 2000;105:359-362. Mehr SS, et al. J Allergy Clin Immunol. 2006;117(2, suppl): Abstract 1177. S305. 21
22
Used another medication to treat episode
Previous reaction improved quickly
Current reaction seemed mild or improved quickly
Rapid progression of reaction
Patient was unsure when to inject or injected too late
Not accessible when reaction occurred
Patient taking another medication that interfered
Not prescribed by physician Not affordable Did not have auto-injector
with them
Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol. 2010;10:354-361. Simons FER, et al. J Allergy Clin Immunol. 2009;124:301-306. 22
23
Antihistamines Antagonize only one of the multiple mediators
in anaphylaxis Take too long to work
23
24
Anaphylaxis is an acute, life-threatening systemic reaction resulting from the sudden release of mediators from mast cells and basophils
These mediators include: Leukotrienes Prostaglandins Histamine Platelet-activating factor Interleukins Others
24 Lieberman P, et al. J Allergy Clin Immunol. 2010;126:477-480.
Jones DH, et al. Ann Allergy Asthma Immunol. 2008;100(5):452-456.
Suppression of Histamine-induced Flare
51.7
79.2
101.2
T50
Min
utes
IM=intramuscular; PO=oral. 25
0
25
50
75
100
125
Fexofenadine IMDiphenhydramine
PODiphenhydramine
Fexofenadine PO (180 mg) Diphenhydramine IM (50 mg) Diphenhydramine PO (50 mg)
Flare Response
Jones DH, et al. Ann Allergy Asthma Immunol. 2008;100(5):452-456.
Perc
ent C
hang
e Fr
om B
asel
ine
100
75
50
25
0
-25
-50
-75
-100 Baseline 30 60 90 120 150 180 210 240 300 360
*P=.01
Minutes Post Medication Administration
*
26
Signs and Symptoms Percent*
Cutaneous Urticaria and angioedema Flushing Pruritus without rash
85-90 45-55
2-5
Respiratory Dyspnea, wheeze Upper airway angioedema Rhinitis
45-50 50-60 15-20
Dizziness, syncope, hypotension 30-35
Abdominal Nausea, vomiting, diarrhea, cramping pain
25-30
Miscellaneous Headache Substernal pain Seizure
5-8 4-6 1-2
27
*Percentages are approximations. Lieberman P, et al. J Allergy Clin Immunol. 2010;126:477-480. 27
Immediate treatment with Epi is imperative
No contraindications Delay = Fatalities Always available Self injector IM Emergency plan
No international consensus: Epinephrine appears underutilized 20-60% use internationally. Corticosteroids are used in Canada, UK and Russia Patient follow-up is lacking: 12-16% Referred for follow-up with Allergy Specialist 0-38% prescribed epi-pen following initial ER visit Discussion focused on fatalities: what about morbidities and complications? Comorbidities? Obesity?
Anaphylaxis is underreported Incidence estimated to be 21 per 100,000 person-years If this is projected as a national average, then approximately
63,000 new cases of anaphylaxis would be reported each year in the United States
Up to 41 M Americans
Yocum et al. Epidemiology of Anaphylaxis in Olmsted County: A population based study. J Allergy Clin Immunol 1999;104:452-456.
Neugut, A et al, 2001.
•Yocum et al. Epidemiology of Anaphylaxis in Olmsted County: A population based study. J Allergy Clin Immunol 1999;104:452-456.
Epidemiologic surveys have reported systemic reactions to insect stings in 1% of children and 3% of adults.
Food-induced anaphylaxis is estimated to occur in 1-3% of children.
Drug reactions are also common with anaphylaxis occurring in approximately 1% of adults.
Radiocontrast media cause anaphylaxis in 0.1% of procedures performed.
Allergen immunotherapy injections cause systemic symptoms in 10-15% of treated patients but anaphylaxis is estimated to occur in 3% of cases.
Increasing reports of latex anaphylaxis over the past 10 years approaching 1% of adults.
Estimates suggest that 5% of adults may have a history of anaphylaxis.
Cutaneous Pruritus, urticaria, angioedema, flushing
Gastrointestinal Nausea, emesis, cramps, diarrhea
Ocular Pruritus, tearing, redness
Genitourinary Urinary urgency, uterine cramp
Cardiovascular Tachycardia then hypotension Shock: ≤ 50% intravascular volume loss Bradycardia (4%) (transient or persistent) Myocardial ischemia
Lower respiratory - bronchoconstriction wheeze, cough, shortness of breath
Upper respiratory Laryngeal/pharyngeal edema Rhinitis symptoms
Uniphasic Biphasic Same manifestations as at presentation recur up
to 8 hours later Reported in up to 20% of cases
Protracted Up to 32 hours May not be prevented by glucocorticoid
Type I hypersensitivity - IgE (Anaphylaxis)
Allergen exposure
Production of allergen-specific IgE
IgE-sensitized mast cells
IgE-mediated mast cell degranulation upon re-exposure to allergen
Complement activation (Anaphylactoid) Type II hypersensitivity Type III hypersensitivity Aggregated Ig Non-immunologic (iodinated dye)
Direct mast cell activation Drugs (e.g. ASA, vancomycin), exercise, cold,
idiopathic
Histamine H1: smooth muscle contraction
vascular permeability H2: vascular permeability H1+H2: vasodilatation, pruritus
Leukotrienes Smooth muscle contraction vascular permeability and dilatation
Nitric Oxide Smooth muscle relaxation vascular permeability and dilatation
Vasovagal syncope
Systemic mastocytosis
Scromboid poisoning
Other causes of shock (hypovolemic, cardiogenic, septic)
Antibiotics and other medications Beta lactams, tetracyclines, sulfas
Foreign proteins Latex, hymenoptera venoms, seminal plasma
Foods Shellfish, legumes, nuts and others
Food-induced anaphylaxis Rapid-onset Multi-organ system involvement Potentially fatal Any food, highest risk: ▪ peanut, nut, seafood, sesame
Food-associated, exercise-induced Associated with a particular food Associated with eating any food
Frequency: ~ 150 deaths / year Risk: Underlying asthma – Delayed epinephrine Symptom denial – Previous severe reaction
History: known allergic food Key foods: peanut / nuts / shellfish Biphasic reaction Lack of cutaneous symptoms in 80%
History of systemic reaction in 0.5% - 3.0% of the population
Positive venom skin test or RAST in 15% - 25% of the population
Transient positive skin test or RAST may occur after uneventful sting
Presence of IgE venom antibody not necessarily predictive of clinical sensitivity
Spontaneous loss of clinical venom sensitivity Adults differ from children Evolution of systemic reactions frequency and severity large local into systemic no predictive markers
Clinical presentation: urticaria/angioedema/ anaphylaxis
Caused by many drugs and biologics Most often due to ß-lactam antibiotics Less common with many non-ß-lactam
antibiotics
Opiates
Radiocontrast media
Colloid volume expanders
Dextran
Mannitol
ASA / NSAIDs
Risk Factor Idiopathic Exercise Latex Radiocontrast
media
Not Risk Factor Penicillin Insulin
Muscle relaxants Hymenoptera
venoms
Age: Most fatalities > 45 yo Gender: Worse in males Constancy of antigen administration Time elapsed since last reaction
10-15% during initial immunotherapy, 1-3% during maintenance
Most in < 20 minutes, but severity worse with later onset
Systemic not preceded or predicted by large local reactions
Related to: dose/vial errors, unstable asthma, seasonal flare, extreme sensitivity, ß blockers, new vial / new extract, rush schedule
Fatal reactions: 58 observed over 25 years: 90% in < 30 minutes
30% due to errors
50% delayed use of epinephrine
50% with acute asthma
25% prior systemic reactions
25% peak pollen season Lockey 1987,1992; Reid 1990, 1992
Canadian Pediatric Surveillance: 81% of events in children were due to food allergies.
Fatal anaphylaxis: ▪ Young children: Cow’s milk ▪ Adolescent: Peanut allergy ▪ Adults: Tree nut; venom, drug
Children are more likely to have respiratory symptoms; adults more likely to have CV compromise.
Wang J and HA Sampson (2007) “Food anaphylaxis.” Clinical and Experimental Allergy 32: 651-660
Airway (laryngeal) and tissue (visceral) edema Pulmonary hyperinflation Tissue eosinophilia Elevated serum tryptase Myocardial injury
Fatalities ≅ 4%
Increased Risk Beta Blockade, severe hypotension, bradycardia,
sustained bronchospasm, poor response to epinephrine
Adrenal Insufficiency
Asthma
Coronary Artery Disease Van der Klauw et al. Clin Exp Allergy 1996;26:1355-1363.
Clinical Features
Serum Tryptase
Serum or urine histamine
Positive prick test or RAST Indicates presence of IgE antibody NOT clinical
reactivity (~50% false positive) Negative prick test or RAST Essentially excludes IgE antibody (>95%)
ID skin test with food Risk of systemic reaction & not predictive Contraindicated
Acute or chronic uticaria or angiodema Asthma attack Foreign body aspiration Food poisoning Vasovagal reaction Anxiety attack Mastocytosis Carcinoid syndrome Pheochromocytoma Serum Sickness Anaphylactoid Scromboid fish Pseudoallergic medication response
Test for specific-IgE antibody Negative: reintroduce food Positive: start elimination diet
Elimination diet No resolution: reintroduce food Resolution
▪ Open / single-blind challenges to “screen” ▪ DBPCFC
History: drug, venom, food, latex reactions Avoidance, Medic-Alert and ID card
Penicillin skin tests & prn desensitization Hymenoptera avoidance & immunotherapy Iodinated Dye Pretreatment Avoid ß blockade in those on immunotherapy or at risk of
Hymenoptera anaphylaxis Immunotherapy in those on ß blockers ACE inhibitors in food / Hymenoptera anaphylaxis
Clinical Manifestations
Prodrome - flushing, pruritus, fatigue
Early - urticaria, angioedema
Established - stridor, GI symptoms, collapse
Late - headache
Precipitating Events: isometric and isotonic exercise; hot environment
Temporally unpredictable
Avoidance of exercise, especially in heat
Avoidance of allergenic foods before exercise
Buddy system-epinephrine
Simons KJ, Simons FER. Curr Opin Allergy Clin Immunol. 2010;10:354-361. Simons FER, et al. J Allergy Clin Immunol. 2009;124:301-306. Simons FER, et al. J Allergy Clin Immunol. 2010;125:S161-S181 Sicherer SH, et al. Pediatrics. 2000;105:359-362. Mehr SS, et al. J Allergy Clin Immunol. 2006;117(2, suppl): Abstract 1177. S305 Lieberman P, et al. J Allergy Clin Immunol. 2010;126:477-480. Hepner MJ, et al. J Allergy Clin Immunol. 1990;86(3 Pt 1):407-411. Müller UR, Haeberli G. J Allergy Clin Immunol. 2005;115:606-610 Korenblat P, et al. Allergy Asthma Proc. 1999;20:383-386. Varghese M, Lieberman P. J Allergy Clin Immunol. 2006;117(2, suppl): Abstract 1178. S305. Haymore BR, et al. Allergy Asthma Proc. 2005;26(5):361-365. Uguz A, et al. Clin Exp Allergy. 2005;35:746-750. Kelso JM. J Allergy Clin Immunol. 2006;117(2):464-465. Mehr S, et al. Clin Exp Allergy. 2009;39(9):1390-1396. Scranton SE, et al. J Allergy Clin Immunol. 2009;123(2):493-498. Tole JW, Lieberman P. Immunol Allergy Clin North Am. 2007;27(2):309-326 Pumphrey RS. Clin Exp Allergy. 2000;30(8):1144-1150 Simons FER, et al. J Allergy Clin Immunol. 2001;108:1040-1044. Jones DH, et al. Ann Allergy Asthma Immunol. 2008;100(5):452-456. Sicherer SH, et al. J Allergy Clin Immunol. 2001;108:128-132. Poulos LM, et al. J Allergy Clin Immunol. 2007;120:878-884 Cianferoni A, et al. Ann Allergy Asthma Immunol. 2004;92:464-468 Webb LM, Lieberman P. Ann Allergy Asthma Immunol. 2006;97(1):39-43